Tumor-Treating Fields + Immunotherapy for Uveal Melanoma

No longer recruiting at 1 trial location

Overseen By Justin Moser, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: HonorHealth Research Institute

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Pacemaker, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for uveal melanoma, a type of eye cancer that often spreads to the liver. Researchers combine Tumor Treating Fields (a device using electric fields to stop cancer cell growth) with two immune-boosting drugs, Ipilimumab (Yervoy) and Nivolumab (Opdivo), to determine if this approach benefits patients. The trial seeks participants with uveal melanoma that has primarily spread to the liver. Participants should not have experienced severe side effects from similar treatments in the past. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you haven't had certain cancer treatments recently and that any side effects from past treatments have resolved. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Tumor Treating Fields (TTF) have been used in treatments for other conditions. The Optune system, part of TTF, has already received FDA approval for treating malignant pleural mesothelioma, a type of cancer. This approval indicates a certain level of safety due to its use in another condition.

Ipilimumab and Nivolumab are drugs that help the immune system fight cancer. They have improved survival rates for patients with metastatic uveal melanoma, meaning many patients have found them helpful.

Although specific safety data for this trial is not yet available, the use of these treatments in other situations provides some reassurance about their safety. In general, researchers closely monitor treatments in early trials to ensure patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for uveal melanoma, like radiation or surgery, focus on directly removing or destroying cancer cells. But the combination of Tumor-Treating Fields (TTF) with immunotherapy drugs like Ipilimumab and Nivolumab works differently. TTF uses electric fields to disrupt cancer cell division, which is a novel approach. Meanwhile, Ipilimumab and Nivolumab are immunotherapy drugs that boost the body's immune system to better identify and attack cancer cells. Researchers are excited about this treatment because it combines these innovative strategies, offering potential synergy that could improve outcomes for patients with this challenging condition.

What evidence suggests that this trial's treatments could be effective for metastatic uveal melanoma?

Research has shown that certain drugs, like Ipilimumab and Nivolumab, help people with advanced uveal melanoma live longer. These drugs enhance the immune system's ability to find and attack cancer cells. In this trial, participants will receive a combination of these immunotherapies with Tumor Treating Fields (TTF), used for cancer that has spread to the liver. TTF employs electric fields to disrupt cancer cell growth, potentially slowing the tumor. A similar device, Optune Lua, has already been approved for treating a different type of cancer, suggesting this technology could be promising. Together, these treatments aim to offer a better way to manage advanced uveal melanoma. ^{1 2 3 4 5}

Who Is on the Research Team?

Justin Moser, MD

Principal Investigator

HonorHealth Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with metastatic uveal melanoma, mainly affecting the liver. Participants must be in good physical condition (ECOG 0-1), have a life expectancy of at least 3 months, and normal organ/marrow function. Women of childbearing potential must test negative for pregnancy and use contraception. Excluded are those with active autoimmune diseases requiring strong medication, recent cancer treatments, or severe reactions to immune checkpoint inhibitors.

Inclusion Criteria

My cancer is a type of eye melanoma that has spread mainly to my liver.

My organs and bone marrow are functioning normally.

I am fully active and can carry on all my pre-disease activities without restriction.

Exclusion Criteria

I had a severe reaction to previous immunotherapy.

I am willing and able to follow the study's procedures.

My side effects from cancer treatments are mostly mild, except for hormone issues being treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tumor Treating Fields in combination with nivolumab and ipilimumab

up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

up to 100 months

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Novocure Optune

Trial Overview The study tests Tumor-Treating Fields targeting liver metastases combined with Nivolumab and Ipilimumab—two immunotherapy drugs—in patients with metastatic uveal melanoma. The goal is to see if this combination improves patient outcomes compared to current treatments.

How Is the Trial Designed?

Group I: TTF Plus Chemotherapy Experimental Treatment 3 Interventions

Novacure Optune with Opdivo and Yervoy

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

HonorHealth Research Institute

Lead Sponsor

Trials

26

Recruited

940+

NovoCure Ltd.

Industry Sponsor

Trials

64

Recruited

6,100+

Ashley Cordova

NovoCure Ltd.

Chief Executive Officer

Bachelor of Science in Material Engineering from Ben-Gurion University of the Negev, Israel

Uri Weinberg

NovoCure Ltd.

Chief Medical Officer since 2020

MD from an unspecified institution

Published Research Related to This Trial

Uveal melanoma and cutaneous melanoma show significant differences in their immune responses, with cutaneous melanoma having a stronger antitumor T-cell response, particularly with a higher presence of CD8(+) T cells compared to the CD4(+) dominant TIL in uveal melanoma.

However, a subset of uveal melanoma patients exhibited robust antitumor T-cell reactivity, especially in tumors lacking melanin pigmentation, suggesting that these patients may benefit from immunotherapies targeting their unique immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of an Immunogenic Subset of Metastatic Uveal Melanoma. Rothermel, LD., Sabesan, AC., Stephens, DJ., et al.[2023]

Immune checkpoint inhibitors (ICIs), specifically PD-1/PD-L1 inhibitors, have a lower risk of treatment-related and nonspecific ophthalmic adverse events compared to chemotherapy, with odds ratios of 0.44 and 0.28 respectively, indicating they are safer options for patients.

However, when PD-1 inhibitors are combined with CTLA-4 inhibitors or chemotherapy, the risk of immune-related adverse events significantly increases, suggesting that combination therapies may lead to higher ocular complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Ophthalmic Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. Hou, YL., Wang, DY., Hu, JX., et al.[2022]

High levels of PD-1 expression in primary uveal melanoma are linked to poorer patient survival and larger tumor size, indicating that PD-1 could serve as a prognostic marker.

Manipulating PD-1 levels in uveal melanoma cell lines showed that increasing PD-1 promotes tumor growth, while reducing PD-1 inhibits it, suggesting that targeting PD-1 may be a promising treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 expression on uveal melanoma induces tumor proliferation and predicts poor patient survival. Jiang, Z., Yan, Y., Dong, J., et al.[2022]

In a retrospective review of 15 patients with metastatic uveal melanoma treated with anti-PD-1 antibodies (pembrolizumab or nivolumab), the best response observed was stable disease in four patients, indicating limited efficacy as no objective responses were recorded.

The treatment was generally well tolerated, with manageable toxicity, and the median progression-free survival was 3 months, while the overall survival was 5 months, suggesting that while the therapy may not be highly effective, it can be safely administered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 antibodies in metastatic uveal melanoma: a treatment option? Bender, C., Enk, A., Gutzmer, R., et al.[2021]

In a study of 39 patients with uveal melanoma treated with ipilimumab, the overall response rate was low at 2.6%, but the combined response plus stable disease rate was 46% at 12 weeks, indicating some potential for disease stabilization.

Ipilimumab was associated with significant immune-related adverse events in 71.8% of patients, with more severe events occurring in those receiving higher doses, but the treatment was deemed to have manageable toxicity and a median overall survival of 9.6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience. Luke, JJ., Callahan, MK., Postow, MA., et al.[2022]

Ipilimumab, an immune checkpoint inhibitor used for metastatic melanoma, can lead to severe ophthalmic immune-related adverse events (irAEs) such as uveitis and hypotony, as demonstrated in a case study of a 69-year-old man who experienced significant vision loss after treatment.

The patient's condition required aggressive management with corticosteroids and surgical interventions, highlighting the need for careful monitoring and follow-up for patients on ipilimumab, especially those with prior glaucoma surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab-related uveitis and refractory hypotony with a flat chamber in a trabeculectomized eye with exfoliation glaucoma: A case report. Funagura, N., Fukushima, S., Inoue, T.[2023]

A rare case of panuveitis occurred in a patient receiving Nivolumab and Ipilimumab for recurrent Small Cell Lung Cancer, highlighting the potential for serious immune-related ocular toxicities from checkpoint inhibitors.

The patient successfully managed the panuveitis with an Ozurdex injection, leading to resolution of inflammation and improved vision, allowing her to continue Nivolumab treatment without recurrence of the eye condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panuveitis in patient on ipilimumab/nivolumab combination for small-cell lung cancer treated with an intravitreal dexamethasone implant. L Hefler, J., M Bailey, L., El Rahi, C., et al.[2021]

A novel immunotherapeutic strategy combining local photodynamic therapy (PDT) with a ROCK inhibitor and PD-1/PD-L1 blockade showed promising results in treating uveal melanoma (UM) by enhancing immune responses and preventing metastasis.

In mouse models, this combination therapy not only reduced primary tumor size but also transformed the tumor microenvironment to promote the infiltration of cytotoxic T cells, leading to improved survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In situ immunogenic clearance induced by a combination of photodynamic therapy and rho-kinase inhibition sensitizes immune checkpoint blockade response to elicit systemic antitumor immunity against intraocular melanoma and its metastasis. Kim, S., Kim, SA., Nam, GH., et al.[2021]

In a nationwide study of patients with metastatic uveal melanoma (UM), the introduction of immune checkpoint inhibitors (ICI) as first-line treatment significantly improved overall survival rates, increasing from 25.0% to 41.9% one year after treatment.

Despite relatively low response rates (7% for anti-PD-1 monotherapy and 21% for combined therapy), median overall survival improved from 7.8 months to 10.0 months, indicating that ICI therapy offers a meaningful benefit for patients with metastatic UM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma. Bol, KF., Ellebaek, E., Hoejberg, L., et al.[2020]

In a study of 41,674 cancer patients, only 3.0% reported ocular adverse events (oAEs) related to immune checkpoint inhibitors, with the most common being vision disorders and uveitis.

Uveitis was found to be significantly more common in melanoma patients receiving the combination of anti-PD-1 and anti-CTLA-4 therapies, with a reporting odds ratio (ROR) of 17.1, indicating a strong association.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular Adverse Events Induced by Immune Checkpoint Inhibitors: A Comprehensive Pharmacovigilance Analysis. Bomze, D., Meirson, T., Hasan Ali, O., et al.[2022]

In a study involving 13 patients with metastatic uveal melanoma treated with ipilimumab, no objective tumor responses were observed, but some patients achieved stable disease, suggesting potential for further investigation.

The treatment was generally well-tolerated, with no severe non-immune adverse events reported, although 23% of patients experienced grade 3 immune-related adverse events that were manageable with steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy. Danielli, R., Ridolfi, R., Chiarion-Sileni, V., et al.[2022]

In a study of 64 patients with metastatic uveal melanoma treated with a combination of CTLA-4 and PD-1 inhibitors, the overall response rate was 15.6%, with a median overall survival of 16.1 months, indicating that this combination therapy may be the most effective option currently available for this difficult-to-treat cancer.

Despite a significant number of patients experiencing severe treatment-related adverse events (39.1%), the tolerability of this combined therapy appears to be better than that seen in trials for cutaneous melanoma, suggesting a potentially safer profile for patients with uveal melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study. Heppt, MV., Amaral, T., Kähler, KC., et al.[2023]

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(25)00365-5/fulltext

How we treat patients with metastatic uveal melanoma Tebentafusp became the first-in-class ImmTAC to improve overall survival in metastatic uveal melanoma patients.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05004025?term=nivolumab%20ipilimumab&viewType=Table&rank=9

Single Arm Trial of Tumor-Treating Fields in Combination ... Tumor Treating Fields targeted to liver metastases may improve outcomes for patients with metastatic uveal melanoma treated with immune checkpoint inhibitors.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05004025

NCT05004025 | Single Arm Trial of Tumor-Treating Fields ... Tumor Treating Fields targeted to liver metastases may improve outcomes for patients with metastatic uveal melanoma treated with immune checkpoint inhibitors.

4. novocure.com novocure.com/novocure-announces-optune-luatm-brand-name-novottf-100ltm-system

Novocure Announces Optune Lua™ as the Brand Name ... Optune Lua, formerly known as NovoTTF-100L, is the first FDA-approved treatment for malignant pleural mesothelioma in over 15 years.

5. withpower.com withpower.com/trial/phase-1-melanoma-9-2021-bef79

Tumor-Treating Fields + Immunotherapy for Uveal Melanoma The use of immune checkpoint inhibitors (ICI) like Ipilimumab and Nivolumab has shown improved survival rates in patients with metastatic uveal melanoma, with a ...